US 9,809,829 B2
Genetically modified host cells and use of same for producing isoprenoid compounds
Jay D. Keasling, Berkeley, CA (US); James Kirby, Drogheda (IE); and Eric M. Paradise, Vienna, VA (US)
Assigned to The Regents of the University of California, Oakland, CA (US)
Filed by The Regents of the University of California, Oakland, CA (US)
Filed on Aug. 4, 2014, as Appl. No. 14/451,056.
Application 14/451,056 is a continuation of application No. 11/571,315, granted, now 8,828,684, previously published as PCT/US2005/026190, filed on Jul. 21, 2005.
Claims priority of provisional application 60/592,009, filed on Jul. 27, 2004.
Prior Publication US 2015/0087042 A1, Mar. 26, 2015
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 15/79 (2006.01); C12N 15/80 (2006.01); C12N 1/15 (2006.01); C12N 1/19 (2006.01); C12P 5/00 (2006.01); C12N 9/10 (2006.01); C12N 15/81 (2006.01); C12P 23/00 (2006.01); C12N 9/04 (2006.01); C12N 9/88 (2006.01)
CPC C12P 5/007 (2013.01) [C12N 9/0006 (2013.01); C12N 9/1085 (2013.01); C12N 9/88 (2013.01); C12N 15/81 (2013.01); C12P 23/00 (2013.01); C12Y 101/01034 (2013.01); C12Y 205/01092 (2013.01); C12Y 402/03024 (2013.01)] 30 Claims
 
1. A genetically modified eukaryotic host cell that produces an isoprenoid or an isoprenoid precursor compound via a mevalonate pathway, the genetically modified eukaryotic host cell comprising genetic modifications comprising:
a) a heterologous nucleic acid, integrated into the host cell's chromosome, encoding an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) to mevalonate;
b) a heterologous nucleic acid, integrated into the host cell's chromosome, encoding farnesyl diphosphate (FPP) synthase,
c) a heterologous nucleic acid, integrated into the host cell's chromosome, to decrease the level of activity of squalene synthase; and
d) a heterologous nucleic acid comprising a nucleotide sequence encoding a terpene synthase,
wherein the genetic modifications provide for production of an isoprenoid or an isoprenoid precursor compound at a level that is at least about 50% higher than the level of the isoprenoid or isoprenoid precursor compound in a control cell not comprising the genetic modifications.